| Laboratory Medicine and Pathobiology --- University of Toronto

Our laboratory is interested in understanding the molecular mechanisms at play in the tug-of-war between viruses and the host. We want to understand how certain retroviruses enter cells and are then antagonized by innate immune molecules. Immunological recognition and restriction of viral pathogens is fundamental for fighting infectious disease.

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Research

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Specifically, our research is focused on three areas:

a) Virus-cell and cell-cell fusion
b) How human innate immune restriction factors target HIV-1 replication and are counteracted by viral antagonists
c) Discovery of anti-viral agents

We employ a combination of X-ray crystallography and small angle X-ray scattering, in addition to other molecular biological and biophysical techniques, to understand these host-pathogen interactions. Crystallographic analysis of viral surface glycoproteins and restriction factors has offered a tremendous wealth of insights into recognition, entry, evasion, restriction, and pathogenesis unobtainable by other methods. Once structures are determined, questions and hypotheses arising will be subsequently tested using biochemical, immunological and virological techniques. The structural and functional data obtained will serve as models for the screening and design of inhibitors radically different than those currently used to treat HIV/AIDS and/or other viral infections. In addition, these studies are likely to lead to the discovery of important model principles to understand how viruses control normal host cellular processes.

Training opportunities are currently available for prospective graduate students through the Department of Laboratory Medicine and Pathobiology. Prospective students are encouraged to contact the PI directly (jeff.lee@utoronto.ca).

Publications

See all Publications: PubMed

JD Cook, A Sultana, and JE Lee. (2017). Structure of the infectious salmon anemia virus receptor complex illustrates a unique binding strategy for attachment. Proc Natl Acad Sci U S A. 114(14): E2929-2936.

H Aydin, A Sultana, S Li, A Thavalingam, and JE Lee. (2016). Molecular architecture of the human sperm izumo1 and egg Juno fertilization complex. Nature. 534(7608):562-5.

KJ Abraham, JN Chan, JS Salvi, B Ho, A Hall, E Vidya, R Guo, SA Killackey, N Liu, JE Lee, GW Brown, and K Mekhail. (2016). Intersection of calorie restriction and magnesium in the suppression of genome-destabilizing RNA-DNA hybrids. Nucleic Acid Res. 44(18):8870-8884.

Y Kano, JD Cook, JE Lee, and M Ohh. (2016). New structural and functional insight into the regulation of Ras. Semin. Cell. Dev. Biol. 58:70-78.

P Heir, T Srikumar, G Bikopoulos, S Bunda, BP Poon, JE Lee, B Raught, and M Ohh. (2016). Oxygen dependent regulation of erthyropoietin receptor turnover and signaling. J Biol Chem. 291(14):7357-72.

JD Cook, H Soto-Montoya, MK Korpela, and JE Lee. (2015). Electrostatic architecture of the ISAV core fusion protein illustrates carboxyl-carboxylate pH sensor. J Biol Chem. 290(30):18495-504.

T Hashiguchi, ML Fusco, ZA Bornholdt, JE Lee, AI Flyak, R Matsuoka, D Kohda, Y Yanagi, M Hammel, JE Crowe Jr, and EO Saphire. (2015). Structural basis of Marburg virus neutralization by a cross-reactive human antibody. Cell. 160(5):904-12.

A Sultana and JE Lee. (2015). Measuring protein-protein and protein-nucleic acid interactions by biolayer interferometry. Curr Protoc Protein Sci. 79:19.25.1-26.

S Bunda, P Heir, T Srikumar, JD Cook, K Burrell, Y Kano, JE Lee, G Zadeh, B Raught, and M Ohh. (2014). Src promotes GTPase activity of Ras via tyrosine 32 phosphorylation. Proc Natl Acad Sci U S A. 111(36):E3785-94.

H Aydin*, M Taylor* and JE Lee. (2014). Structure-guided analysis of the human APOBEC3-HIV restrictome. Structure. 22(5):668-84.

H Aydin, D Al-Khooly and JE Lee. (2014). Influence of hydrophobic and electrostatic residues on SARS-coronavirus S2 protein stability: insights into mechanisms of general viral fusion and inhibitor design. Protein Science. 23(5):603-17.

KK Siu, A Sultana, FC Azimi and JE Lee. (2013). Structural determinants of HIV-1 Vif susceptibility and DNA binding in APOBEC3F. Nature Communications. 4 (4), 2593.

H Aydin, JD Cook and JE Lee. (2013). Crystal structures of beta- and gamma-retroviral fusion proteins reveal a role for electrostatic stapling in viral entry. Journal of Virology. 88 (1)143-53.

H Aydin, BM Smrke and JE Lee. (2013). Structure of a retroviral fusion protein from a virus that undergoes a two-step viral entry mechanism. FASEB Journal. 27 5072-82.

JD Cook and JE Lee. (2013). The secret life of viral entry glycoproteins: moonlighting in immune evasion. PLoS Pathogens. 9 (5) e1003258. 1-5.

P Heir, RI Sufan, SN Greer, BP Poon, JE Lee, and M Ohh. (2013). DCNL1 functions as a substrate sensor and acivator of cullin2-RING ligase. Mol Cell Biol 33 (8),1621-31.

H Aydin*, FC Azimi*, JD Cook*, and JE Lee. (2012). A convenient and general expression platform for the production of secreted proteins from human cells. Journal of Visualized Experiments. 65. pii: 4041.

JE Lee, ML Fusco, and EO Saphire. (2009). An efficient platform for screening expression and crystallization of glycoproteins in human cells. Nature Protocols. 4 (4), 592-604

JE Lee and EO Saphire. (2009). Neutralizing Ebolavirus: structural insights into the envelope glycoprotein and antibodies targeted against it. Current Opinions in Structural Biology. 19, 1-10.

JE Lee, ML Fusco, AJ Hessell, WB Oswald, DR Burton, and EO Saphire. (2008). Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor. Nature. 454, 177-182. (featured cover article)

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